Safety of outpatient closed-loop control: first randomized crossover trials of a wearable artificial pancreas

Boris P Kovatchev, Eric Renard, Claudio Cobelli, Howard C Zisser, Patrick Keith-Hynes, Stacey M Anderson, Sue A Brown, Daniel R Chernavvsky, Marc D Breton, Lloyd B Mize, Anne Farret, Jérôme Place, Daniela Bruttomesso, Simone Del Favero, Federico Boscari, Silvia Galasso, Angelo Avogaro, Lalo Magni, Federico Di Palma, Chiara Toffanin, Mirko Messori, Eyal Dassau, Francis J Doyle 3rd, Boris P Kovatchev, Eric Renard, Claudio Cobelli, Howard C Zisser, Patrick Keith-Hynes, Stacey M Anderson, Sue A Brown, Daniel R Chernavvsky, Marc D Breton, Lloyd B Mize, Anne Farret, Jérôme Place, Daniela Bruttomesso, Simone Del Favero, Federico Boscari, Silvia Galasso, Angelo Avogaro, Lalo Magni, Federico Di Palma, Chiara Toffanin, Mirko Messori, Eyal Dassau, Francis J Doyle 3rd

Abstract

Objective: We estimate the effect size of hypoglycemia risk reduction on closed-loop control (CLC) versus open-loop (OL) sensor-augmented insulin pump therapy in supervised outpatient setting.

Research design and methods: Twenty patients with type 1 diabetes initiated the study at the Universities of Virginia, Padova, and Montpellier and Sansum Diabetes Research Institute; 18 completed the entire protocol. Each patient participated in two 40-h outpatient sessions, CLC versus OL, in randomized order. Sensor (Dexcom G4) and insulin pump (Tandem t:slim) were connected to Diabetes Assistant (DiAs)-a smartphone artificial pancreas platform. The patient operated the system through the DiAs user interface during both CLC and OL; study personnel supervised on site and monitored DiAs remotely. There were no dietary restrictions; 45-min walks in town and restaurant dinners were included in both CLC and OL; alcohol was permitted.

Results: The primary outcome-reduction in risk for hypoglycemia as measured by the low blood glucose (BG) index (LGBI)-resulted in an effect size of 0.64, P = 0.003, with a twofold reduction of hypoglycemia requiring carbohydrate treatment: 1.2 vs. 2.4 episodes/session on CLC versus OL (P = 0.02). This was accompanied by a slight decrease in percentage of time in the target range of 3.9-10 mmol/L (66.1 vs. 70.7%) and increase in mean BG (8.9 vs. 8.4 mmol/L; P = 0.04) on CLC versus OL.

Conclusions: CLC running on a smartphone (DiAs) in outpatient conditions reduced hypoglycemia and hypoglycemia treatments when compared with sensor-augmented pump therapy. This was accompanied by marginal increase in average glycemia resulting from a possible overemphasis on hypoglycemia safety.

Trial registration: ClinicalTrials.gov NCT01714505 NCT01727817 NCT01742741.

© 2014 by the American Diabetes Association.

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Source: PubMed

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